Flow nanoparticle measurement device and method of determining nanoparticle using the same

ABSTRACT

A flow nanoparticle measurement device according to an embodiment of the present disclosure includes a flow cell configured to form a flow path through which a liquid sample flows, a laser generator configured to generate a first laser beam and irradiate the first laser beam to the flow cell, a plurality of detectors disposed in the flow cell and configured to detect a shock wave of a plasma generated in the flow cell by the first laser beam and generate a detection signal, and a controller configured to obtain the detection signal from the plurality of detectors and determine a type and a size of nanoparticles contained in the liquid sample in response to the detection signal.

CROSS-REFERENCE TO RELATED APPLICATIONS AND CLAIM OF PRIORITY

This application claims the priority benefit of Korean Patent Application No. 10-2020-0136343 filed on Oct. 20, 2020 in the Korean Intellectual Property Office (KIPO), the entire disclosure of which is incorporated by reference herein.

BACKGROUND 1. Field

The present disclosure relates to a flow nanoparticle measurement device and a method of determining nanoparticles using the same. More specifically, the present disclosure relates to a measurement device for measuring a tiny amount of nanoparticles existing in a sample with flow.

The present disclosure relates to a highly sensitive detection method capable of detecting a sample with a low concentration of ppt level of 100 nm or less when analyzing a high-purity chemical, such as a liquid chemical, i.e., a solvent, in a state with flow rate. The present disclosure relates to a measurement device that collects and analyzes signals generated by generating an induced plasma from nano-sized particles by a light source with specific energy.

2. Description of the Related Art

Various organic and inorganic chemicals used in a manufacturing process of products requiring high precision, such as displays and semiconductors, require higher purity chemicals than the present in order to prevent a reduction in manufacturing yield, and high-level analysis techniques have been developed and newly applied in order to check the quality of high purity chemicals. Among them, the importance of particle analysis is gradually increasing. Because even small particles of 10-nanometer level may affect the yield reduction and high integration of the semiconductor manufacturing process, the development of a stable analysis method for quality control is required, and the scalability of the technology must also be ensured so that it is possible to analyze even the causes of defects that may occur in the manufacturing process.

In general, a substance that is uniformly dispersed in a liquid in a molecular or ionic state is called a solution. A state in which minute particles, which are larger than normal molecules or ions and have a diameter of about 1 nm to 1000 nm, are dispersed in such a solution without aggregation or precipitation is called a colloidal state, and those in the colloidal state are called colloid.

Research on microcolloids present in the solution is focused on obtaining information on the physical and chemical properties of a substance to be analyzed or improving the detection power of a separation analyzer. The analysis of colloidal particles until recently has a limit of 100 nm in size, and there is a need to develop the technology in that a high concentration sample is required for accurate analysis of colloidal particles of 100 nm or less.

A method of measuring colloidal nanoparticles generally uses a light scattering analysis method for checking the size of a particle using light scattering intensity. However, when fine nanoparticles less than 100 nm in size are measured, the probability of detection at a low concentration rapidly decreases even if scattering light is generated, and thus it is difficult to obtain a reliable result. Further, there is a limit that the concentration of particles has to be parts per million (ppm) or more. The light scattering intensity increases as the particle size increases, whereas the light scattering area decreases as the particle size decreases. Therefore, it is difficult to measure the particle size due to a reduction in the light scattering intensity. Since a relatively large number of particles have to be able to contribute to scattering, the sensitivity is greatly reduced at a concentration less than ppm.

SUMMARY

One aspect of the present disclosure provides a flow nanoparticle measurement device and a method of determining nanoparticles using the same capable of detecting particles with a part per trillion (PPT) concentration of 100 nm or less.

Another aspect of the present disclosure provides a dynamic flow nanoparticle measurement device and a method of determining nanoparticles using the same for improving measurement reliability for the measurement of nanoparticles.

Another aspect of the present disclosure provides a flow nanoparticle measurement device and a method of determining nanoparticles using the same that use a cell with a shape designed so that it can be detected in a sample with flow, and include a flow controller consisting of a piston pump and a magnetic valve so that the flow can be controlled without eddy, unlike a general nanoparticle analysis method.

Another aspect of the present disclosure provides a flow nanoparticle measurement device for determining a type and a size of nanoparticles based on natural frequencies and amplitudes of nanoparticles detected by a plurality of detectors.

In order to achieve the above-described and other objects of the present disclosure, in one aspect of the present disclosure, there is provided a flow nanoparticle measurement device including a flow cell configured to form a flow path through which a liquid sample flows; a laser generator configured to generate a first laser beam and irradiate the first laser beam to the flow cell; a plurality of detectors disposed in the flow cell and configured to detect a shock wave of a plasma generated in the flow cell by the first laser beam and generate a detection signal; and a controller configured to obtain the detection signal from the plurality of detectors and determine a type and a size of nanoparticles contained in the liquid sample in response to the detection signal.

In another aspect of the present disclosure, there is provided a flow nanoparticle measurement method (S200, S300) using a flow nanoparticle measurement device including a flow cell forming a flow path through which a liquid sample flows, a laser generator generating a pulsed laser beam and irradiating a first laser beam split from the pulsed laser beam to the flow cell, and a plurality of detectors disposed in a flow direction of the liquid sample and detecting a shock wave of a plasma generated in the flow cell to generate a detection signal, the flow nanoparticle measurement method including a step (S210, S310) of measuring an amplitude and a frequency of the shock wave in response to the detection signal; a step (S220, S320) of calculating an amplitude ratio based on the amplitude and a natural frequency detected per the plurality of detectors; and a step (S230, S330) of specifying a type of nanoparticles contained in the liquid sample from the measured natural frequency and determining a size of the nanoparticles based on the calculated amplitude ratio.

According to one aspect of the present disclosure, the present disclosure can measure nanoparticles of a liquid sample of which a flow is controlled.

According to one aspect of the present disclosure, the present disclosure can reduce a measurement error that may occur when calculating the number of nanoparticles using a measurement value of a very small area in a stationary cell by measuring the nanoparticles in a state where the liquid sample flows, and thus can improve the reliability of nanoparticle measurement.

According to one aspect of the present disclosure, the present disclosure can improve the detection probability of nanoparticles and thus improve the reliability of nanoparticle detection.

An object of the present disclosure is to improve detection power capable of detecting particles of 100 nm or less and a trace amount of samples of a low concentration by controlling a flow rate using a flow control device in order to detect an instantaneously generated signal in plasma detection.

The present disclosure can determine the size of nanoparticles based on an amplitude ratio by detecting, by a plurality of detectors, a shock wave signal resulting from the plasma generation.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are included to provide a further understanding of the disclosure and are incorporated in and constitute a part of the disclosure, illustrate embodiments of the disclosure and together with the description serve to explain the principle of the disclosure.

FIG. 1 schematically illustrates a flow nanoparticle measurement device according to an embodiment of the present disclosure.

FIG. 2 illustrates configurations related to a flow device of a flow nanoparticle measurement device according to an embodiment of the present disclosure.

FIGS. 3A and 3B illustrate a flow cell of a flow nanoparticle measurement device according to an embodiment of the present disclosure.

FIG. 4 illustrates an example of a flow controller of a flow nanoparticle measurement device according to an embodiment of the present disclosure.

FIG. 5 is a flow chart illustrating a flow nanoparticle measurement method (S100) according to an embodiment of the present disclosure.

FIG. 6 illustrates an operation depending on time in a flow nanoparticle measurement device according to an embodiment of the present disclosure.

FIG. 7 illustrates an operation depending on time in a flow nanoparticle measurement device according to another embodiment of the present disclosure.

FIG. 8 schematically illustrates that plasma is generated by a pulsed laser beam in a flow nanoparticle measurement device according to an embodiment of the present disclosure.

FIG. 9 is a block diagram illustrating a controller of a flow nanoparticle measurement device according to an embodiment of the present disclosure.

(a) and (b) of FIG. 10 are graphs illustrating a frequency and an amplitude of shock waves detected by a plurality of detectors that is one configuration of a flow nanoparticle measurement device according to an embodiment of the present disclosure.

FIG. 11 is a flow chart illustrating a method (S200) of determining a type and a size of nanoparticles according to an embodiment of the present disclosure.

FIG. 12 is a flow chart illustrating a method (S300) of determining a type and a size of nanoparticles according to another embodiment of the present disclosure.

DETAILED DESCRIPTION

The detailed description and specific examples such as embodiments of the present disclosure are given merely by way of example, since various changes and modifications within the spirit and scope of the present disclosure will become apparent to those skilled in the art from the detailed description.

Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts or components.

Terms used in the present disclosure are used to explain embodiments and are not intended to limit and/or restrict the present disclosure. A singular expression can include a plural expression as long as it does not have an apparently different meaning in context. In the present disclosure, terms “include” and “have” should be understood to be intended to designate that illustrated features, numbers, steps, operations, components, parts or combinations thereof are present and not to preclude the existence of one or more different features, numbers, steps, operations, components, parts or combinations thereof, or the possibility of the addition thereof.

The terms including an ordinal number such as “first”, “second”, etc. may be used to describe various components, but the components are not limited by such terms. The terms are used only for the purpose of distinguishing one component from other components. For example, a first component may be referred to as a second component without departing from the spirit and scope of the present disclosure, and a second component may be referred to as a first component in the same manner. The term “and/or” includes a combination of items related to plurality or some of items related to plurality.

In addition, term such as “part”, “device”, “block”, “member”, and “module” may refer to a unit processing at least one function or operation. For example, the terms may mean at least one hardware such as field-programmable gate array (FPGA)/application specific integrated circuit (ASIC), at least one software stored in a memory, or at least one process processed by a processor.

Reference will now be made in detail to embodiments of the disclosure, examples of which are illustrated in the accompanying drawings. The accompanying drawings illustrate embodiments of the present disclosure and are used to help easily understand various technical features, and it should be understood that embodiments presented herein are not limited by the accompanying drawings.

Although the present disclosure may detect light emitted by generating an induced plasma from microparticles using a laser, the present disclosure is described focusing on a method of analyzing shock waves and the size of plasma. This is referred to as a laser-induced breakdown detection (LIBD) technique and is a particle analysis method that can obtain information such as size, concentration, distribution, and composition of nanoparticles by detecting intensity and distribution of an induced plasma generated by focusing a high energy pulsed laser on particles existing in an aqueous solution using various detection methods. Hence, this method has a lower detection limit as the particle size decreases, compared to the existing light scattering method, transmission electron microscope, atomic force microscope, etc. It is reported that this method can theoretically measure up to 1 nano-sized particles, and this method is a nanoparticle analysis method of low concentration where a concentration range is ppt concentration range.

The existing laser-induced breakdown detection method measures shock waves and plasma scintillation generated when an induced plasma is generated. The shock wave is acoustically measured, and the plasma scintillation is measured by attaching a camera near the cell. However, even if plasma is generated by impurities other than nanoparticles of a target to be measured during the measurement of the shock waves and the plasma scintillation, it may be detected and recognized as the shock wave or the scintillation. Alternatively, plasma may be generated again by continuously receiving energy from the generated plasma, and may be detected as a noise.

The present disclosure proposes a method for detecting an induced shock wave generated in a liquid sample with flow using a flow rate control device, and quantifying it to classify the sizes. When the size of nanoparticles for the sample with flow is determined using the control device, the present disclosure can achieve a higher detection limit than the existing detection and non-contact real-time measurement by measuring a range of a specific area, and can obtain a reliable result by changing a measurement path in real time. In addition, the present disclosure can measure nanoparticles for all the samples rather than measuring only some of the samples as in the existing measurement method, thereby improving the reliability of the result.

An area irradiated with an actual laser light source is measured while maintaining a very high linear velocity in a thin flow path in order to measure a sample flowing in a very small area. In this instance, an image of plasma is greatly distorted due to the high speed. In some cases, since it is difficult to detect due to a change in a contrast ratio, reproducibility or detection sensitivity is reduced. In order to improve this, the present disclosure tries to detect an image in an instantaneous static state using a flow pulse such as a pulsed laser. To this end, there is a need for a flow cell that can flow without eddy and is manufactured so that a laser beam is incident and generates a maximum signal value. In addition, a flow controller that can control the speed for a temporary static state controls the linear speed by temporarily operating an internal piston pump with a pulse width. More specifically, the flow controller may be configured to control a flow rate of the liquid sample to correspond to the pulse width. The present disclosure can increase the detection probability and sensitivity of plasma and improve the accompanying problem such as distortion or contrast ratio and shock wave sensitivity to thereby effectively improve the reliability of result by detecting the plasma signal value generated by the pulsed laser beam in the instantaneous static state of the liquid sample by the flow controller.

A flow nanoparticle measurement device may use the LIBD method. The LIBD method allows a pulsed laser beam with a time width of several nanoseconds to be incident through a lens and uses a principle of a laser-induced plasma generated in a focal region of the lens when the laser beam is incident. More specifically, when the pulsed laser beam is irradiated to nanoparticles, an energy level of the nanoparticles becomes an excited state, and then energy is released to exist in a stable state, i.e., a ground state (or excited state). Due to the energy released in this process, plasma or shock waves are generated in the nanoparticles.

In this instance, a phenomenon of generating plasma or shock wave is called a breakdown phenomenon, which requires the minimum energy required for particles to generate a plasma, and this is called a threshold energy. The threshold energy depends on a phase of a material because an ionization energy required for each material is different. The threshold energy requires the highest energy in a gaseous state, and decreases in the order of liquid and solid states.

The energy of the laser beam required to generate the laser-induced plasma increases in the order of solid, liquid, and gas. Therefore, when the appropriate laser beam energy is used, a laser-induced plasma state can be generated by breaking down only solid particles in an aqueous solution.

The concentration and size of nanoparticles can be analyzed by taking advantage of the characteristic that the breakdown probability varies depending on the particle concentration under the condition of a fixed laser beam energy and the characteristic that the threshold energy of the laser beam required for the breakdown varies depending on the particle size.

The flow nanoparticle measurement device can compensate for problem and reliability that may occur when particles are detected according to the above theory. In most particle analysis devices, contamination may occur in the process of collecting and analyzing a sample, and there is a possibility that the value may be mistaken for a value due to a contaminant. Since a high-purity material is easily contaminated, the device was developed to allow sample injection and direct analysis by minimizing contamination using a specially designed flow cell.

FIG. 1 schematically illustrates a flow nanoparticle measurement device according to an embodiment of the present disclosure.

A flow nanoparticle measurement device 1 may include a laser generator 10 and a flow device 20. The flow device 20 may include a flow cell 30, an inlet portion 41, and an outlet portion 42. A liquid sample may enter the flow device 20 through the inlet portion 41. The liquid sample entering the flow device 20 may pass through the flow cell 30. The liquid sample passing through the flow cell 30 may be discharged to the outside through the outlet portion 42.

The laser generator 10 may include a laser generating device 12, an optical diaphragm 13, a mirror 14, a beam splitter 16, an energy detector 17, a lens 18, and a beam block 19.

The laser generating device 12 may generate a pulsed laser beam B. A wavelength of the pulsed laser beam B is not limited. The pulsed laser beam B may be irradiated using Q-switching. The pulsed laser beam B may be repeatedly irradiated with a pulse of a predetermined period T1 (see FIG. 6 ). That is, the laser generating device 12 may irradiate the pulsed laser beam B so that on/off is repeated with a first period T1. The pulsed laser beam B generated by the laser generating device 12 may include Nd:YAG pulsed laser beam with a wavelength of 532 nm. However, the present disclosure is not limited thereto, and a type and an energy magnitude of the laser beam irradiated by the laser generating device 12 may be variously applied.

The optical diaphragm 13 may be provided at one side of the laser generating device 12 and may adjust a diameter of the pulsed laser beam that is emitted by the laser generating device 12 and then is incident. A diameter of the laser beam emitted by the laser generating device 12 may be variably adjusted by the optical diaphragm 13.

The mirror 14 is provided on a path of the pulsed laser beam B and may convert the path of the pulsed laser beam B. In addition, at least one mirror is disposed on the path of the pulsed laser beam B and thus can allow only the pulsed laser beam B with a desired wavelength to reach the flow cell 30.

The beam splitter 16 may adjust the path of the pulsed laser beam B. The beam splitter 16 may split the pulsed laser beam B into several paths at a predetermined ratio. The beam splitter 16 may adjust intensity of the laser beam branched from the pulsed laser beam B.

The beam splitter 16 may adjust a path of at least a part beam B1 of the incident pulsed laser beams B to be directed toward the flow cell 30. For example, the beam splitter 16 may split the pulsed laser beam B into a first laser beam B1 and a second laser beam B2. That is, the pulsed laser beam B incident on the beam splitter 16 may be split into the first laser beam B1 and the second laser beam B2. The optical characteristics of the first laser beam B1 may correspond to the optical characteristics of the pulsed laser beam B. For example, the first laser beam B1 may be a pulse laser with a predetermined period. For example, a pulse period of the first laser beam B1 may be a first period T1 (see FIGS. 6 and 7 ).

For example, a traveling direction of the first laser beam B1 may be different from a traveling direction of the pulsed laser beam B incident on the beam splitter 16. For example, the traveling direction of the first laser beam B1 may be perpendicular to the traveling direction of the pulsed laser beam B incident on the beam splitter 16. For example, a traveling direction of the second laser beam B2 may be the same as or parallel to the traveling direction of the pulsed laser beam B incident on the beam splitter 16.

For example, power of the first laser beam B1 generated by the beam splitter 16 may be less than power of the pulsed laser beam B incident on the beam splitter 16. For example, the power of the first laser beam B1 generated by the beam splitter 16 may be the same as power of the second laser beam B2 generated by the beam splitter 16.

The energy detector 17 may measure the power (or energy) of the second laser beam B2. The energy detector 17 may face the beam splitter 16. The second laser beam B2 generated by the beam splitter 16 may be incident on the energy detector 17. The traveling direction of the second laser beam B2 may form an angle with the traveling direction of the first laser beam B1.

The power (or energy) of the first laser beam B1 may correspond to the power (or energy) of the second laser beam B2. Thus, a power (or energy) measurement value measured by the energy detector 17 may be used to calculate the power (or energy) of the first laser beam B1. For example, if the power of the first laser beam B1 is the same as the power of the second laser beam B2, the power measured by the energy detector 17 may be the power of the first laser beam B1.

The lens 18 may be disposed between the beam splitter 16 and the flow cell 30. For example, the first laser beam B1 generated by the beam splitter 16 may be incident on the lens 18. The optical characteristics of the first laser beam B1 may be changed while passing through the lens 18. For example, a focus of the first laser beam B1 passing through the lens 18 may be one point of the flow cell 30.

In other words, the lens 18 may adjust an irradiation area and a focal length of the first laser beam B1 incident on the flow cell 30. The focal length of the first laser beam B1 may refer to a distance between the focus of the first laser beam B1 passing through the lens 18 and the lens 18. The lens 18 can improve the detectability of nanoparticles by adjusting the irradiation area of the first laser beam B1 incident on the flow cell 30. A focal length of the lens 18 may be adjusted based on a Gaussian distribution with respect to the generation of induced plasma of nanoparticles by the first laser beam B1. The focal length of the first laser beam B1 may be set to 10 to 40 mm, but is not limited thereto.

A location at which the induced plasma is generated in the flow cell 30 may correspond to a location at which the first laser beam B1 collides with the nanoparticles. A liquid sample flowing in the flow cell 30 may have a unique refractive index. Thus, the focal length of the first laser beam B1 may vary depending on a type of the liquid sample flowing in the flow cell 30. For the measurement of various liquid samples, it may be necessary to appropriately adjust the focal length. To this end, the location at which the induced plasma is generated in the flow cell 30 may be controlled by adjusting a distance between the lens 18 and the flow cell 30 depending on the type of the liquid sample. The distance between the lens 18 and the flow cell 30 may be adjusted by a controller 70. For example, the controller 70 may control the position of the lens 18 by moving the lens 18.

The beam block 19 may face the flow cell 30. The flow cell 30 may be positioned between the lens 18 and the beam block 19. For example, the first laser beam B1 may be incident on the beam block 19 after passing through the flow cell 30. The beam block 19 may suppress the travel of the incident first laser beam B1. For example, the beam block 19 may block (or shield) the incident first laser beam B1.

The flow cell 30 may form a flow path F. In FIG. 1 , the flow path F may be indicated by a dotted line. The flow path F may be formed outside and inside the flow cell 30. The flow path F may indicate a path through which the liquid sample flows. The flow path F may indicate a direction in which the liquid sample flows. In this context, the flow path F may be referred to as a “flow direction”.

The flow path F, in a narrow sense, may refer to a path through which the liquid sample flows in the flow cell 30. The flow cell 30 may include a cell inlet 32 and a cell outlet 34.

The flow path F formed inside the flow cell 30 may extend from the cell inlet 32 and lead to the cell outlet 34. For example, the liquid sample may enter the inside of the flow cell 30 through the cell inlet 32 and may be discharged to the outside of the flow cell 30 through the cell outlet 34.

The flow path F, in a broad sense, may refer to a path through which the liquid sample flows within the flow device 20. The flow path F formed inside the flow device 20 may extend from the inlet portion 41 and lead to the outlet portion 42.

The flow nanoparticle measurement device 1 may include a detector 60, a flow controller 50, and the controller 70. The description of the detector 60, the flow controller 50, and the controller 70 may be included in the description of FIG. 2 .

FIG. 2 illustrates configurations related to a flow device of a flow nanoparticle measurement device according to an embodiment of the present disclosure. FIGS. 3A and 3B illustrate a flow cell of a flow nanoparticle measurement device according to an embodiment of the present disclosure.

The flow device 20 may be configured to flow the liquid sample.

The flow cell 30 may be configured to flow the liquid sample in the flow cell 30. The flow cell 30 may include the cell inlet 32 into which the liquid sample is introduced, and the cell outlet 34 from which the liquid sample is discharged. The flow cell 30 may be formed of a material containing a quartz, but is not limited thereto. For example, the flow cell 30 may be formed of a material including a polymer material such as acrylic.

It is described and illustrated that a shape of the flow cell 30 has a rectangular external shape, but the shape is not limited. When the flow cell 30 is composed of a rectangular cell, the detector 60 to be described later may be positioned in a direction perpendicular to an outer surface of the rectangular cell, or positioned in a direction inclined from the outer surface of the rectangular cell at a predetermined angle. However, the shape of the flow cell 30 and the arrangement of the detector 60 according to the shape of the flow cell 30 are not limited.

The flow cell 30 may be configured so that the liquid sample flows inside the flow cell 30. At least a part of the flow cell 30 may be made of a light transmission material so that the first laser beam B1 is irradiated to the liquid sample positioned in the flow cell 30.

The flow cell 30 may include a flow portion 36 in which the liquid sample flows. The flow portion 36 may be a space formed in the flow cell 30. The flow path F in a narrow sense may be formed by the flow portion 36. The flow portion 36 may extend from the cell inlet 32 and lead to the cell outlet 34. For example, the flow portion 36 may be connected to an opening formed in the cell inlet 32. For example, the flow portion 36 may be connected to an opening formed in the cell outlet 34. The cell outlet 34 may be spaced apart from the cell inlet 32.

The flow portion 36 may be formed to extend from the cell inlet 32, bend and extend again, and lead to the cell outlet 34. For example, the flow portion 36 may form a bent shape. An end of the flow portion 36 may be connected to the cell inlet 32, and another end of the flow portion 36 may lead to the cell outlet 34.

An inner diameter of the flow portion 36 may be formed within 10 mm, but is not limited thereto. The size and shape of the inner diameter of the flow portion 36 may be variously applied. For example, as illustrated in FIG. 3A, a cross section of the flow portion 36 may have a rectangular shape. Alternatively, as illustrated in FIG. 3B, the cross section of the flow portion 36 may has a circular shape.

When the flow portion 36 is formed in the circular cross section as illustrated in FIG. 3B, a distance between the flow portion 36 and the detector 60 may be configured to be the same even if a direction in which the detector 60 is arranged with respect to the flow portion 36 is changed. Hence, restrictions on the arrangement of the detector 60 can be reduced, and thus the reliability of detection results can be improved.

In addition, when the flow portion 36 is formed in the rectangular cross section as illustrated in FIG. 3A, the first laser beam B1 may be irradiated in a direction perpendicular to the flow portion 36 or a plasma signal may be received. Hence, the distortion such as refraction of the signal can be reduced. Through this configuration, more accurate detection results can be obtained.

In addition, when the flow portion 36 is formed in the rectangular cross section as illustrated in FIG. 3A, a larger flow path can be formed with respect to the same width, and thus a smooth flow of the liquid sample can be derived. However, the shape of the flow portion 36 is not limited. For example, at least a part of the flow portion 36 may be formed in a curved surface, and the rest of the flow portion 36 may be formed in a flat surface. That is, the cross section of the flow portion 36 may be formed in a shape in which a curved surface and a polygon are combined. When a portion of the flow portion 36 is formed in a curved surface, the detection intensity can be maximized, and furthermore, the generation of bubbles in the liquid sample according to the flow rate can be minimized.

The size of the inner diameter of the flow portion 36 may be uniformly formed over the entire flow path F, and may vary along the flow path F. More specifically, the flow portion 36 is divided into a plurality of sections, and each section may have a different inner diameter, or a main flow portion 38 of the flow portion 36 to be described later may have a different inner diameter and a different shape from other sections of the flow portion 36. The size and shape of the inner diameter of the flow portion 36 are not limited.

The flow portion 36 may include the main flow portion 38 transmitting the first laser beam B1. The main flow portion 38 may form at least a part of a flow space 37 in which the liquid sample flows. The first laser beam B1 may be irradiated to the main flow portion 38. The flow space 37 may form a flow path through which the liquid sample flows in one direction. The main flow portion 38 may form a part of the flow space 37. The main flow portion 38 transmitting the first laser beam B1 may be a part of the flow portion 36 or may be all of the flow portion 36. As illustrated in FIGS. 3A and 3B, a portion before the flow portion 36 is bent may be the main flow portion 38. However, the present disclosure is not limited thereto. For example, a portion after the flow portion 36 is bent may be the main flow portion 38, and the entire flow portion 36 may be defined as the main flow portion 38. The position of the main flow portion 38 on the flow portion 36 is not limited.

For example, as illustrated in FIG. 2 , the main flow portion 38 may be formed to extend from the cell inlet 32 in one direction. For another example, the main flow portion 38 may be formed to extend from the cell outlet 34 in one direction.

The first laser beam B1 may be irradiated to the flow path of the liquid sample passing the main flow portion 38. More specifically, the first laser beam B1 may be irradiated to the center of the flow path of the liquid sample passing the main flow portion 38. However, the irradiation position of the pulsed laser beam B1 with respect to the main flow portion 38 is not limited thereto.

The first laser beam B1 may pass through the main flow portion 38. In other words, the main flow portion 38 is formed to extend in one direction and may pass the path of the first laser beam B1. For example, in the main flow portion 38, a flow direction F of the liquid sample and the irradiation direction of the first laser beam B1 may be perpendicular to each other. That is, the extending direction of the main flow portion 38 and the incident direction of the first laser beam B1 may be perpendicular to each other. The main flow portion 38 may be formed to extend from the cell inlet 32 in one direction.

For the irradiation of the first laser beam B1, at least a part of the flow cell 30 including the main flow portion 38 may include a light transmission material. Hence, the first laser beam B1 may pass through the flow cell 30 and may be irradiated to the liquid sample passing the main flow portion 38.

However, the present disclosure is not limited thereto, and the flow direction F of the liquid sample and the irradiation direction of the pulsed laser beam B1 may be adjusted to a predetermined angle. An angle formed by the flow direction F and the irradiation direction of the pulsed laser beam B1 may be differently applied depending on the type of the detector 60.

The flow device 20 may include the inlet portion 41 and the outlet portion 42.

The liquid sample may pass through the inlet portion 41 and may be introduced into the flow cell 30. After the liquid sample is discharged from the flow cell 30, the liquid sample may be discharged to the outside of the flow device 20 through the outlet portion 42.

The flow device 20 may be connected to a reservoir in which the liquid sample is stored. For example, the inlet portion 41 and the outlet portion 42 may be connected to the reservoir. The liquid sample may be introduced into the flow device 20 from the reservoir through the inlet portion 41. The liquid sample may be introduced into the reservoir from the flow device 20 through the outlet portion 42. However, the present disclosure is not limited thereto, and the inlet portion 41 and the outlet portion 42 may be connected to independent reservoirs, respectively.

The flow device 20 may include the flow controller 50.

The flow controller 50 may be disposed on the path of the liquid sample. The flow controller 50 may control a flow rate and a flow amount of the liquid sample passing the flow cell 30. The controller 70 may control the flow rate or flow amount of the liquid sample passing the flow cell 30 by controlling the flow controller 50.

As illustrated in FIG. 1 , the flow controller 50 may be positioned on a path between the flow cell 30 and the outlet portion 42. That is, since the flow controller 50 is disposed downstream in the flow path of the liquid sample, contamination of the liquid sample to be measured can be minimized. However, the arrangement of the flow controller 50 is not limited.

For example, the flow controller 50 may be positioned on a path between the flow cell 30 and the inlet portion 41. The flow controller 50 is configured to control the flow rate of the liquid sample flowing in the flow cell 30, and may satisfy this if it is disposed at a position at which the liquid sample is not contaminated.

The flow controller 50 may control the flow rate so that a predetermined flow amount of the liquid sample is positioned in the main flow portion 38 in a stationary state. That is, the flow controller 50 may control the flow rate so that the liquid sample repeatedly flows with a pulse of a predetermined period T2 (see FIG. 6 ). In other words, the flow controller 50 may control the flow rate of the liquid sample so that the liquid sample flows in the form of a pulse wave of a second period T2 (see FIGS. 6 and 7 ).

The flow controller 50 may be configured so that the flow state and the flow stop state of the liquid sample alternately operate in the second period T2 (see FIGS. 6 and 7 ). The flow state is a state in which the liquid sample flows through the flow portion 36, and the flow stop state may indicate that the liquid sample is disposed in a state in which the flow is stopped in the flow portion 36.

As illustrated in FIG. 6 , the flow controller 50 may be configured so that the liquid sample alternately flows between the flow state and the flow stop state in the form of a pulse. When the flow controller 50 controls the liquid sample to be in the flow state, the liquid sample may flow through the flow portion 36 at a first flow velocity V1. FIG. 6 illustrates that the first flow velocity V1 has a constant velocity, for convenience of description, but a magnitude and change of the first flow velocity V1 are not limited thereto. When the flow controller 50 controls the liquid sample to be in the flow stop state, the flow of the liquid sample in the flow portion 36 may be stopped.

The flow controller 50 may repeatedly operate in the flow state and the flow stop state based on the signal received by the controller 70, and may mechanically operate repeatedly in the flow state and the flow stop state. A method of implementing the operation of the flow controller 50 is not limited. This may be satisfied if the flow of the liquid sample is controlled by the flow controller 50.

The flow operation of the liquid sample by the flow controller 50 may correspond to irradiation of the first laser beam B1 by the laser generating device 12. For example, the first period T1 of the first laser beam B1 and the second period T2 of the flow controller 50 may be the same. For example, the flow controller 50 may control the flow rate of the liquid sample passing the flow cell 30 so that the second period T2 of the flow controller 50 is the same as the period T1 of the first laser beam B1.

Referring to FIG. 6 , a time at which the flow stop state of the liquid sample starts may be synchronized with a time at which the output of the first laser beam B1 becomes a second output P2. Referring to FIG. 7 , the time at which the output of the first laser beam B1 becomes the second output P2 may be later than the time, at which the flow stop state of the liquid sample starts, by a first delay time d1.

When the flow controller 50 stops the flow of the liquid sample passing the main flow portion 38, the laser generator 10 may generate an induced plasma in the nanoparticles in the liquid sample by irradiating the first laser beam B1 to the main flow portion 38 of the flow cell 30.

Afterwards, when the flow controller 50 controls the liquid sample to be in the flow state, the flow controller 50 may flow the liquid sample, in which the induced plasma is generated by flowing the liquid sample, to the downstream, and may introduce the liquid sample, in which the induced plasma is not generated, into the main flow portion 38. When the liquid sample flows, the laser generator 10 may control the output of the first laser beam B1 so that the induced plasma is not generated in the liquid sample.

When the flow controller 50 stops the flow of the liquid sample passing the main flow portion 38, the pulsed laser beam B1, as the second output P2, is irradiated to the main flow portion 38 of the flow cell 30 by the laser generator 10, and thus the induced plasma may be generated in the nanoparticles in the liquid sample.

The present disclosure can measure the nanoparticles of the flowing liquid sample and improve the reliability of the nanoparticle measurement by repeating the processes.

The flow device 20 may be configured such that the flow amount of the liquid sample passing the main flow portion 38 in the flow state is equal to or greater than an amount of the liquid sample positioned in the main flow portion 38 in the flow stop state. Through this configuration, the liquid sample exposed to the first laser beam B1 of the second output P2 is again exposed to the first laser beam B1 of the second output P2, thereby preventing an error in the nanoparticle measurement.

The flow device 20 may include a separation unit (not shown) for separating the nanoparticles in the liquid sample before the liquid sample containing the nanoparticles is introduced into the flow cell 30. The separation unit may be disposed between the flow cell 30 and the inlet portion 41 to separate nanoparticles from the liquid sample introduced into the flow cell 30. The separation of nanoparticles may be performed based on the type of nanoparticles or the size of the nanoparticles.

FIG. 4 illustrates an example of a flow controller of a flow nanoparticle measurement device according to an embodiment of the present disclosure.

The flow controller 50 may be configured to control the flow of the liquid sample. The flow controller 50 may operate in response to a control signal received from the controller 70.

The flow controller 50 may include a single piston pump. However, the present disclosure is not limited thereto. This may be satisfied if the flow controller 50 is configured to receive a signal from the controller 70 and control the flow rate of the liquid sample so that the signal corresponds to the pulse of the pulsed laser beam B. As an example, the flow controller 50 may include a magnetic valve for controlling the flow amount and the flow rate of the liquid sample.

The flow controller 50 may include a cam 51 that rotates according to the first cycle T1 (see FIGS. 6 and 7 ) of the first laser beam B1 (see FIG. 1 ), a cylinder 54, a piston 52 that is positioned inside the cylinder 54 and moves, and a connecting rod 53 having one end that is rotatably connected to the cam 51, and other end that is rotatably connected to the piston 52 and transfers a rotational force of the cam 51 to the piston 52. An inner space 55 may indicate a space formed in the cylinder 54. A boundary of the inner space 55 may be determined by the piston 52. The piston 52 may be disposed in the inner space 55. The piston 52 may be coupled to the cylinder 54 to reciprocate in one direction.

The cam 51 may rotate about a rotation shaft 51 a. The one end of the connecting rod 53 may be rotatably connected to the cam 51 at a location spaced apart from the rotation shaft 51 a. When the cam 51 rotates, the piston 52 may reciprocate inside the cylinder 54 through the connecting rod 53.

The flow controller 50 may adjust a flow period of the liquid sample by controlling a rotation speed of the cam 51. That is, the flow controller 50 may adjust a period for the flow state and the flow stop state of the liquid sample by controlling the rotation speed of the cam 51. The flow amount of the liquid sample may be controlled by the rotation speed of the cam 51, an arrangement relationship between the rotation shaft 51 a of the cam 51 and the connecting rod 53, an internal volume of the cylinder 54, and the like. For example, the flow amount of the liquid sample may be controlled by adjusting the flow amount of the liquid sample.

The flow controller 50 may include valves 56 a and 56 b. In this embodiment, the valves 56 a and 56 b may include a pair of valves 56 a and 56 b. One valve 56 a of the pair of valves 56 a and 56 b may be disposed at a liquid sample inlet of the cylinder 54. The other valve 56 b of the pair of valves 56 a and 56 b may be disposed at a liquid sample outlet of the cylinder 54.

The valve 56 a disposed at the liquid sample inlet of the cylinder 54 may be referred to as an inlet valve 56 a. The valve 56 b disposed at the liquid sample outlet of the cylinder 54 may be referred to as an outlet valve 56 b. The inlet valve 56 a may be connected to the flow cell 30 (see FIG. 1 ). The outlet valve 56 b may be connected to the outlet portion 42 (see FIG. 1 ).

The valves 56 a and 56 b may include a backflow prevention valve. For example, the backflow prevention valve may be a check valve. The inlet valve 56 a allows the liquid sample to be introduced into the inner space 55, but may suppress the liquid sample from being discharged to the outside of the inner space 55. The outlet valve 56 b allows the liquid sample to be discharged to the outside of the inner space 55, but may suppress the liquid sample from being introduced into the inner space 55.

The piston 52, the inlet valve 56 a, and the outlet valve 56 b may be connected to the inner space 55. In other words, the piston 52, the inlet valve 56 a, and the outlet valve 56 b may form a portion of a boundary of the inner space 55.

When the inner space 55 of the cylinder 54 is pressurized by the piston 52, the inlet valve 56 a may be closed, and the outlet valve 56 b may be opened. In this process, the liquid sample in the inner space 55 may be discharged to the outside of the flow controller 50 through the outlet valve 56 b. When the inlet valve 56 a is closed, the flow of the liquid sample positioned further upstream than the flow controller 50 may be stopped. That is, when the inner space 55 of the cylinder 54 is pressurized by the piston 52, the flow of the liquid sample in the flow cell 30 may be stopped. When the inner space 55 of the cylinder 54 is pressurized by the piston 52, it may mean that the inner space of the cylinder 54 is reduced by the piston 52.

On the contrary, when the piston 52 operates in the opposite direction to a pressurization direction, the outlet valve 56 b may be closed, and the inlet valve 56 a may be opened. When the piston 52 operates in a direction opposite to the pressurization direction, it may mean that the inner space 55 of the cylinder 54 is increased by the piston 52. In this process, the liquid sample outside the cylinder 54 may be introduced into the inner space 55 of the cylinder 54 through the opened inlet valve 56 a.

When the inner space 55 of the cylinder 54 is increased by the piston 52, the inlet valve 56 a may be opened. When the inlet valve 56 a is opened, the liquid sample may be introduced into the inner space 55 of the cylinder 54 through the inlet valve 56 a. When the liquid sample is introduced into the inner space 55 of the cylinder 54 through the inlet valve 56 a, the liquid sample positioned in the flow cell 30 may flow. That is, when the inner space 55 of the cylinder 54 is increased by the piston 52, the liquid sample positioned in the flow cell 30 may flow.

It is illustrated and described that the flow cell 30 is disposed further upstream than the flow controller 50, by way of example, but the present disclosure is not limited thereto. When the flow cell 30 is disposed further downstream than the flow controller 50, the above operation may be performed reversely.

That is, the movement of the piston 52 in the pressurization direction may allow the liquid sample in the flow cell 30 to operate in the flow state, and the movement of the piston 52 in the opposite direction to the pressurization direction may allow the liquid sample in the flow cell 30 to stop flowing. In other words, for example, the inlet valve 56 a may be connected to the inlet portion 41 (see FIG. 1 ), and the outlet valve 56 b may be connected to the flow cell 30 (see FIG. 1 ). For example, when the inner space 55 of the cylinder 54 is pressurized by the piston 52, the liquid sample in the flow cell 30 (see FIG. 1 ) may flow. For example, if the piston 52 moves in the opposite direction to the direction in which the cylinder 54 is pressurized, the liquid sample in the flow cell 30 (see FIG. 1 ) may not flow.

Through this process, the flow controller 50 may control the flow of the liquid sample with a predetermined period.

Referring to FIGS. 1 to 4 , the flow nanoparticle measurement device 1 may include the detector 60.

The nanoparticles included in the liquid sample may be in a plasma state by the first laser beam B1. The detector 60 may detect a shock wave or scintillation generated in this process. The detector 60 may detect various signals generated in the plasma. The detector 60 may detect at least one of a spectrum of an element, a shock wave, an image of plasma, heat, and sound.

The detector 60 may include a shock wave detector that measures a laser-induced shock wave accompanied when a laser-induced plasma is generated. The detector 60 may include a scintillation detector 60 that detects scintillation accompanied when the laser-induced plasma is generated. When the induced plasma is generated in the nanoparticles by the first laser beam B1, characteristics of the laser induced plasma may vary depending on the size of the nanoparticles.

The shock wave detector may include at least one of a piezoelectric element and a microphone. The signal measured by the shock wave detector may be amplified by a lock-in amplifier.

The scintillation detector may include a CCD camera. The scintillation detector 60 may further include a notch filter disposed on an optical path toward the CCD camera in order to control a measurement error caused by scattered light. As illustrated in FIG. 1 , each of the shock wave detector and the scintillation detector may be disposed adjacent to the flow cell 30. At least one of the shock wave detector and the scintillation detector may be disposed adjacent to the flow cell 30.

The detector 60 may acquire information about the nanoparticles through the detection of the shock wave or the scintillation. Information about the nanoparticles may include the number and/or the size of nanoparticles.

The detector 60 may be disposed inside the flow cell 30, or may be disposed outside the flow cell 30 as illustrated in FIG. 1 . In addition, a plurality of detectors 60 may be disposed around the flow cell 30. The controller 70 may correct a detection value based on a distance from a location, at which the induced plasma is generated inside the flow cell 30, to the detector 60. The controller 70 may correct the detection value based on an angle between a direction toward the detector 60 at a location, at which the induced plasma is generated inside the flow cell 30, and the irradiation direction of the first laser beam B1. The type of the detector 60 is not limited, and the detector 60 may include various detectors such as a thermal sensor.

The flow nanoparticle measurement device 1 may include the controller 70.

The controller 70 may control the overall operation of the flow nanoparticle measurement device 1. For example, the controller 70 may control the laser generating device 12 and the flow controller 50. The controller 70 may control the laser generating device 12 to control the first cycle T1 (see FIGS. 6 and 7 ) and/or the output of the first laser beam B1. In addition, the controller 70 may control the flow controller 50 to control the second period T2 (see FIGS. 6 and 7 ) or the flow time of the liquid sample.

The control of the laser generating device 12 and the flow controller 50 by the controller 70 may be performed independently of each other. That is, the controller 70 may control each of the laser generating device 12 and the flow controller 50.

The controller 70 may move the lens 18 with respect to the flow cell 30 to adjust the focal length of the first laser beam B1.

The controller 70 may obtain information about the nanoparticles from the detector 60.

The controller 70 may pre-process the signal transmitted from the detector 60. The controller 70 amplifies the signal detected by the detector 60 using the lock-in amplifier and can remove a noise of a low frequency band of 100 Hz or less using a band filter. The filtered signal may be converted into a digital signal through a converter. The converted signal may be subjected to Fast Fourier Transformation (FFT) in real time by extracting signal values of some sections according to conditions. Through this process, the controller 70 may convert the signal from a function of time to a function of frequency and analyze a frequency component of the shock wave generated by the plasma. The controller 70 may determine the type, size, or number of nanoparticles based on the frequency component and the amplitude size converted from the detected shock wave.

The magnitude of the induced plasma increases as the size of the particles increases under the same output condition, and hence the size of the shock wave may also increase. Based on the frequency component and the amplitude size of the shock wave, the controller 70 may determine the type, size, or number of nanoparticles.

The controller 70 may determine the size or the number of nanoparticles based on the number and the size of scintillations detected by the scintillation detector.

The controller 70 may measure a concentration of the nanoparticles in the liquid sample based on the flow amount of the liquid sample flowing by the flow controller 50 and information on the nanoparticles detected by the detector 60.

The operation of the flow nanoparticle measurement device according to the present disclosure is described below.

FIG. 5 is a flow chart illustrating a flow nanoparticle measurement method (S100) according to an embodiment of the present disclosure. FIG. 6 illustrates an operation depending on time in a flow nanoparticle measurement device according to an embodiment of the present disclosure.

In the flow chart illustrated in FIG. 5 , the method is described by dividing the method into a plurality of steps, but at least some of the steps may be performed in a different order, performed together in combination with other steps, omitted, sub-divided into sub-steps, or performed by adding one or more steps that are not illustrated.

In FIG. 6 , the second output P2 of the first laser beam B1 may be greater than the first output P1. For example, the first output P1 may be zero. The controller 70 may control the output of the first laser beam B1 over time.

Referring to FIGS. 1 to 5 , the flow nanoparticle measurement device 1 may be configured to measure nanoparticles contained in the flowing liquid sample. The controller 70 may control the laser generating device 12 and the flow controller 50.

The flow device 20 may flow the liquid sample containing the nanoparticles to the main flow portion 38 of the flow cell 30. More specifically, the flow device 20 may introduce the liquid sample into the flow cell 30 through the cell inlet 32 and discharge the liquid sample to the outside of the flow cell 30 through the cell outlet 34. The flow rate of the liquid sample flowing through the flow device 20 may be controlled by the flow controller 50.

Referring to FIGS. 1 to 6 , the flow controller 50 may control the flow rate of the liquid sample so that a predetermined flow amount of the liquid sample is positioned in the main flow portion 38 in a stationary state. That is, the flow controller 50 may be configured to repeatedly flow the liquid sample with the second cycle T2.

The pulsed laser beam B generated by the laser generating device 12 may be split into a first laser beam B1 and a second laser beam B2 by the beam splitter 16. The first laser beam B1 may pass through the lens 18 and may be irradiated to the main flow portion 38 of the flow cell 30. The first laser beam B1 may be repeatedly irradiated with a pulse of the first period T1.

A flow nanoparticle measurement method S100 according to an embodiment of the present disclosure may include a step S110 of irradiating a pulsed laser beam to the liquid sample flowing in the flow cell 30. In the step S110, the pulsed laser beam irradiated to the liquid sample may be the first laser beam B1. In the step S110, the controller 70 may control an output of the first laser beam B1 and irradiate the pulsed laser beam to the liquid sample.

The first period T1 of the first laser beam B1 may be the same as a period of the pulsed laser beam B. The first period T1 of the first laser beam B1 may be the same as the second period T2 of the flow controller 50. The flow controller 50 may control the flow rate of the liquid sample passing the flow cell 30 to correspond to a period of the pulsed laser beam B. For example, a time at which the flow stop state of the liquid sample starts may be synchronized with a time at which the output of the first laser beam B1 becomes the second output P2. For example, a time at which the flow state of the liquid sample starts may be synchronized with a time at which the output of the first laser beam B1 becomes the first output P1.

Through this, when the flow of the liquid sample passing the main flow portion 38 is stopped by the flow controller 50, the first laser beam B1 may be irradiated to the main flow portion 38 of the flow cell 30 to generate plasma in the nanoparticles in the liquid sample.

The flow nanoparticle measurement method S100 according to an embodiment of the present disclosure may include a step S120 of obtaining a detection signal using a detector. The first laser beam B1 may generate plasma or shock waves in the nanoparticles of the liquid sample stopped by the flow controller 50. The detector 60 may detect the generated plasma or shock waves to generate a detection signal. The detection signal may include information on the shock waves. In the step S120, the controller 70 may obtain the detection signal using the detector 60.

The flow nanoparticle measurement method S100 according to an embodiment of the present disclosure may include a step S130 of calculating concentration information of the liquid sample. In the step S130, the controller 70 may calculate the concentration information of nanoparticles contained in the liquid sample based on the flow rate of the liquid sample controlled by the flow controller 50 and the detection signal obtained from the detector 60.

The controller 70 may be configured to control the flow controller 50 so that the liquid sample repeats the flow state and the flow stop state with a predetermined period, and control the laser generator 10 so that the first laser beam B1 is irradiated with a predetermined period. Hence, the method can improve the reliability of the nanoparticle measurement by measuring the nanoparticles of the flowing liquid sample.

FIG. 7 illustrates an operation depending on time in a flow nanoparticle measurement device according to another embodiment of the present disclosure.

Referring to FIGS. 1 to 7 , the flow nanoparticle measurement device 1 may be configured to measure the nanoparticles contained in the flowing liquid sample.

The first period T1 of the first laser beam B1 may be the same as the second period T2 of the flow controller 50.

In addition, a start time of the first period T1 of the first laser beam B1 may be delayed by the first delay time d1 from a start time of the second period T2 of the flow controller 50. In other words, a start time at which the first laser beam B1 operates as the second output P2 may be delayed by the first delay time d1 from a start time at which the flow velocity of the liquid sample becomes zero. Through this, after the flow of the liquid sample is stopped by the flow controller 50 and the first delay time d1 has elapsed, the first laser beam B1 may be irradiated to the flow cell 30.

A start time at which the flow velocity of the liquid sample becomes the first flow velocity V1 may be delayed by a second delay time d2 from a start time at which the first laser beam B1 becomes the first output P1. Through this, after the first laser beam B1 is irradiated to the flow cell 30 and the second delay time d2 has passed, the liquid sample may flow at the first flow velocity V1 and may be discharged from the flow cell 30.

Time for which the flow velocity of the liquid sample is maintained at zero during the second period T2 may be more than time for which the first laser beam B1 operates as the second output P2 during the first period T1. Hence, the first laser beam B1 is irradiated to the nanoparticles in which the induced plasma is not formed, and the induced plasma can be stably generated.

FIG. 8 schematically illustrates that plasma is generated by a pulsed laser beam in a flow nanoparticle measurement device according to an embodiment of the present disclosure.

Referring to FIG. 8 , a plurality of detectors 60 may be provided. A plurality of detectors 60 a, 60 b, and 60 c may be disposed at the flow cell 30. For example, the plurality of detectors 60 a, 60 b, and 60 c may be disposed adjacent to the flow portion 36, and may detect a shock wave resulting from plasma generated in the flow portion 36.

The arrangement of the plurality of detectors 60 a, 60 b, and 60 c with respect to the flow portion 36 is not limited to the arrangement illustrated in FIG. 8 . For example, at least a part of the plurality of detectors 60 a, 60 b, and 60 c may be disposed to be exposed to the flow space 37 of the flow portion 36, or may be disposed in the flow cell 30 to be spaced apart from the flow portion 36 at a predetermined distance.

A shock wave signal may be generated by detecting the shock waves by the detectors 60 a, 60 b, and 60 c. The shock wave signal (or information) may be converted into a signal regarding an amplitude and a frequency by a shock wave analysis unit 180.

The plurality of detectors 60 a, 60 b, and 60 c may be disposed to be spaced apart from each other along the flow direction F of the liquid sample. When the plurality of detectors 60 a, 60 b, and 60 c are disposed to be spaced apart from each other at a predetermined distance, the shock waves resulting from the generation of plasma may be detected by the plurality of detectors 60 a, 60 b, and 60 c by varying a magnitude of the amplitude.

FIG. 8 illustrates that three detectors are disposed, by way of example. However, the present disclosure is not limited thereto. This may be satisfied if at least two detectors are disposed. For convenience of description, the plurality of detectors 60 a, 60 b, and 60 c may include a first detector 60 a, a second detector 60 b disposed further downstream in the flow direction F of the liquid sample than the first detector 60 a, and a third detector 60 c disposed further downstream in the flow direction F than the second detector 60 b.

The first detector 60 a may be disposed adjacent to a position S at which plasma is generated by the irradiation of the first laser beam B1. The position S at which the plasma is generated may be set by the irradiation direction of the first laser beam B1 with respect to the flow portion 36.

The first detector 60 a may be disposed in a radial direction of the position S at which the plasma is generated. However, the position of the first detector 60 a is not limited. For example, this may be satisfied if the first detector 60 a is disposed adjacent to the position S at which the plasma is generated. The plurality of detectors 60 a, 60 b, and 60 c are arranged at a predetermined distance along the flow direction F of the liquid sample and can accurately detect shock waves resulting from the generation of plasma by varying a position and/or an angle from the plasma generation. The plurality of detectors 60 a, 60 b, and 60 c can also minimize distortion of the detection result due to the generation of noise.

When a distance between the plasma generation position S and the detectors 60 a, 60 b, and 60 c is relatively short, bubbles may be generated during detection for a long time. The bubbles may obstruct a detection element from detecting shock waves. In addition, when the distance between the plasma generation position S and the detectors 60 a, 60 b, and 60 c is relatively long, a reflected wave by an outer surface of the flow portion 36 or the surface of the liquid sample may be detected to cause the distortion in the detection result.

The plurality of detectors 60 a, 60 b, and 60 c may include a piezoelectric element in which a width, a length, and a height are 2 mm. The arrangement of the plurality of detectors 60 a, 60 b, and 60 c may be adjusted in nanometers, and thus the shock waves may be detected with a high resolution in consideration of the plasma generation position S.

FIG. 9 is a block diagram illustrating a controller of a flow nanoparticle measurement device according to an embodiment of the present disclosure. (a) and (b) of FIG. 10 are graphs illustrating a frequency and an amplitude of shock waves detected by a plurality of detectors that is one configuration of a flow nanoparticle measurement device according to an embodiment of the present disclosure.

Although three or more detectors may be disposed as described above, an embodiment will be described as including the first and second detectors 60 a and 60 b for convenience of description. The detector 60 may include the third detector 60 c and more detectors.

Referring to FIGS. 9 and 10 , a controller 170 may analyze nanoparticles based on shock waves detected by the plurality of detectors 60 a and 60 b.

The controller 170 may include a shock wave analysis unit 180.

The shock wave analysis unit 180 may analyze shock waves detected by the plurality of detectors 60 a and 60 b. The shock wave analysis unit 180 may convert a signal transmitted from the detector 60 into a function related to frequency and amplitude as illustrated in FIG. 10 . (a) of FIG. 10 illustrates that a shock waves detected by the first detector 60 a is converted into a parameter related to frequency and amplitude, and (b) of FIG. 10 illustrates that a shock wave detected by the second detector 60 b is converted into a parameter related to frequency and amplitude.

The shock wave analysis unit 180 may include a frequency measurement unit 182 measuring a natural frequency and an amplitude measurement unit 184 measuring an amplitude.

The frequency measurement unit 182 may measure a frequency at which an amplitude occurs. In other words, the frequency measurement unit 182 may specify a frequency corresponding to a specific amplitude. One frequency among the frequencies specified by the frequency measurement unit 182 may be defined as a natural frequency. For example, the natural frequency may indicate a frequency corresponding to a local peak amplitude.

The frequency measurement unit 182 may specify at least one natural frequency from a shock wave signal detected by each of the plurality of detectors 60 a and 60 b. The frequency measurement unit 182 may define, as the natural frequency, overlapping frequencies f1 and f2 among the frequencies specified in the plurality of detectors 60 a and 60 b, in order to remove a noise generated during the plasma generation process.

The amplitude measurement unit 184 may measure an amplitude at the natural frequency measured by the frequency measurement unit 182.

The controller 170 may include an amplitude ratio calculator 186 and a nanoparticle determination unit 188.

The amplitude ratio calculator 186 may calculate a ratio of amplitudes at the natural frequency. For example, the amplitude ratio calculator 186 may calculate an amplitude ratio of natural frequencies per the plurality of detectors 60 a and 60 b.

The amplitude ratio calculator 186 may calculate the amplitude ratio of the natural frequencies per the plurality of detectors 60 a and 60 b. If there is a plurality of natural frequencies of nanoparticles, the amplitude measured by the amplitude measurement unit 184 may be different for each natural frequency.

The amplitude ratio calculator 186 may calculate a first amplitude ratio that is a ratio of amplitude magnitudes A1 a and A2 a at the plurality of natural frequencies f1 and f2 measured by the first detector 60 a, and a second amplitude ratio that is a ratio of amplitude magnitudes Alb and A2 b at the plurality of natural frequencies f1 and f2 measured by the second detector 60 b. For example, the first amplitude ratio may be a ratio of the amplitude magnitude A1 a at the first natural frequency f1 to the amplitude magnitude A2 a at the second natural frequency f2 in the first detector 60 a. For example, the second amplitude ratio may be a ratio of the amplitude magnitude Alb at the first natural frequency f1 to the amplitude magnitude A2 b at the second natural frequency f2 in the second detector 60 b. The amplitude magnitude may indicate a magnitude of the amplitude.

The nanoparticle determination unit 188 may determine the type and the size of nanoparticle based on the natural frequencies measured by the frequency measurement unit 182 and the amplitude ratio calculated by the amplitude ratio calculator 186.

The nanoparticle determination unit 188 may specify the type of nanoparticles based on the natural frequencies measured by the frequency measurement unit 182. In addition, the nanoparticle determination unit 188 may determine the size of the specified nanoparticles based on changes in the amplitude ratio.

That is, the nanoparticle determination unit 188 may compare data on the natural frequency for each nanoparticle pre-stored in the controller 170 with the natural frequency calculated by the frequency measurement unit 182 to specify the type of nanoparticles. The nanoparticle determination unit 188 may compare data on the first and second amplitude ratios for each nanoparticle pre-stored in the controller 170 with the first and second amplitude ratios calculated by the amplitude ratio calculator 186 to determine a size of the matched nanoparticles. Through this, the nanoparticle determination unit 188 may determine the type and size of the nanoparticles.

FIG. 11 is a flow chart illustrating a method (S200) of determining a type and a size of nanoparticles according to an embodiment of the present disclosure.

Referring to FIGS. 1 to 11 , plasma is generated in the nanoparticles by the first laser beam B1, and a shock wave is generated in this process.

Since the plurality of detectors 60 a and 60 b are spaced apart from each other along the flow direction F of the liquid sample, the same shock wave may be detected by varying a distance between the plurality of detectors 60 a and 60 b and a shock wave generation position.

The shock wave analysis unit 180 may analyze an electrical signal of the shock wave detected by the plurality of detectors 60 a and 60 b. The shock wave analysis unit 180 may convert the electrical signal of the shock wave into a parameter related to frequency and amplitude.

The frequency measurement unit 182 of the shock wave analysis unit 180 may measure the common natural frequencies f1 and f2 in the first and second detectors 60 a and 60 b. For example, in (a) and (b) of FIG. 10 , the frequency measurement unit 182 may define the first natural frequency f1 as 8 kHz and define the second natural frequency f2 as 22 kHz from the shock waves detected by the first and second detectors 60 a and 60 b.

The method S200 of determining the type and the size of the nanoparticles according to an embodiment of the present disclosure may include a step S210 of measuring an amplitude and a frequency in a shock wave. In the step S210, the controller 70 may measure the amplitude and the frequency of the shock wave based on a detection signal. In other words, in the step S210, the controller 70 may generate spectrum information of the amplitude depending on the frequency from the detection signal.

In the step S210, the amplitude measurement unit 184 of the shock wave analysis unit 180 may measure a magnitude of the amplitude at the natural frequencies f1 and f2. For example, as illustrated in (a) of FIG. 10 , the amplitude measurement unit 184 may measure the amplitude magnitude A1 a at the first natural frequency f1 as 0.015 and measure the amplitude magnitude A2 a at the second natural frequency f2 as 0.16. Further, as illustrated in (b) of FIG. 10 , the amplitude measurement unit 184 may measure the amplitude magnitude Alb at the first natural frequency f1 as 0.012 and measure the amplitude magnitude A2 b at the second natural frequency f2 as 0.004.

The method S200 of determining the type and the size of the nanoparticles according to an embodiment of the present disclosure may include a step S220 of calculating an amplitude ratio at the natural frequencies per the plurality of detectors based on the measured amplitudes and natural frequencies.

In the step S220, the amplitude ratio calculator 186 may calculate a first detector amplitude ratio and a second detector amplitude ratio based on the analysis result of the shock wave analysis unit 180. For example, referring to FIG. 10 , the amplitude ratio calculator 186 may calculate the first detector amplitude ratio as 0.015:0.16 and calculate the second detector amplitude ratio as 0.012:0.004 based on the magnitudes of the amplitude measured by the amplitude measurement unit 184. The detector amplitude ratio may indicate at least one of the first detector amplitude ratio and the second detector amplitude ratio. The “amplitude ratio per detector” may indicate the detector amplitude ratio.

The method S200 of determining the type and the size of the nanoparticles according to an embodiment of the present disclosure may include a step S230 of specifying the type of nanoparticles from the measured natural frequency and determining the size of the nanoparticles based on the amplitude ratio per detector.

In the step S230, the nanoparticle determination unit 188 may determine the type and the size of the nanoparticles. The nanoparticle determination unit 188 may specify the type of nanoparticles based on the measured natural frequencies f1 and f2.

In the step S230, the nanoparticle determination unit 188 may determine the size of the nanoparticles based on the amplitude ratio for the specified nanoparticles calculated by the amplitude ratio calculator 186. That is, the nanoparticle determination unit 188 may specify the type of nanoparticles from the measured natural frequency, and compare the amplitude ratios of the first and second detectors calculated by the amplitude ratio calculator 186 with pre-stored data on the amplitude ratios of the first and second detectors for each type of nanoparticles to determine the size of the specified nanoparticles.

The present disclosure can determine more accurately a type and a size of nanoparticles by varying the distance between the plurality of detectors and the shock wave and determining the nanoparticles based on the change in the amplitude ratio per the plurality of detectors through this. The present disclosure can also improve the reliability of the determination results by using the detection results from the plurality of detectors.

The controller 170 includes the shock wave analysis unit 180, and the shock wave analysis unit 180 may include the frequency measurement unit 182 measuring the natural frequency and the amplitude measurement unit 184 measuring the amplitude.

The controller 170 may include the amplitude ratio calculator 186 and the nanoparticle determination unit 188.

The amplitude ratio calculator 186 may calculate a ratio of magnitudes of the amplitudes. The amplitude ratio calculator 186 may calculate an amplitude ratio per natural frequency in the plurality of detectors 60 a and 60 b.

The amplitude ratio calculator 186 may calculate the amplitude ratio per the natural frequencies f1 and f2 in the plurality of detectors 60 a and 60 b. When the natural frequency of the nanoparticles is one or more, the magnitude of the amplitude measured by the amplitude measurement unit 184 may be detected for each natural frequency.

The amplitude ratio calculator 186 may calculate the amplitude ratio for each of the natural frequencies f1 and f2. That is, the amplitude ratio at the first natural frequency may indicate a ratio of the amplitude magnitude A1 a at the first natural frequency f1 measured by the first detector 60 a to the amplitude magnitude Alb at the first natural frequency f1 measured by the second detector 60 b. Further, the amplitude ratio at the second natural frequency may indicate a ratio of the amplitude magnitude A2 a at the second natural frequency f2 measured by the first detector 60 a to the amplitude magnitude A2 b at the second natural frequency f2 measured by the second detector 60 b. The amplitude ratio at the natural frequency may indicate at least one of a first natural frequency amplitude ratio and a second natural frequency amplitude ratio.

Since the natural frequency amplitude ratio is calculated for each natural frequency, if there is a plurality of natural frequencies, a plurality of amplitude ratios may be calculated. Further, if there is one natural frequency, one natural frequency amplitude ratio may be calculated.

The nanoparticle determination unit 188 may determine the type and the size of nanoparticles based on the natural frequency measured by the frequency measurement unit 182 and the amplitude ratio calculated by the amplitude ratio calculator 186.

The nanoparticle determination unit 188 may specify the type of nanoparticles based on the natural frequency measured by the frequency measurement unit 182. The nanoparticle determination unit 188 may also specify the size of nanoparticles matched to the amplitude ratio calculated by the amplitude ratio calculator 186 based on changes in the pre-stored amplitude ratio per natural frequency. That is, the nanoparticle determination unit 188 may compare pre-stored data on the natural frequency for each nanoparticle with the natural frequency calculated by the frequency measurement unit to specify the type of nanoparticles, and may compare pre-stored data on the amplitude ratio for each natural frequency with the amplitude ratio calculated by the amplitude ratio calculator 186 to determine the size of the matched nanoparticles.

When one nanoparticle has a plurality of natural frequencies, the nanoparticle determination unit 188 may compare the amplitude ratio per the plurality of natural frequencies with pre-stored data to determine the size of the matched nanoparticles. Through this, the nanoparticle determination unit 188 may determine the type and the size of nanoparticles.

FIG. 12 is a flow chart illustrating a method (S300) of determining a type and a size of nanoparticles according to another embodiment of the present disclosure.

Plasma is generated from nanoparticles contained in the liquid sample by the pulsed laser beam B1, and a shock wave is generated in this process.

The plurality of detectors 60 a and 60 b are disposed to be spaced apart from each other along the flow direction F of the liquid sample, and thus the same shock wave may be detected by varying a distance from a shock wave generation position.

The shock wave analysis unit 180 may analyze an electrical signal of the shock wave detected by the plurality of detectors 60 a and 60 b. The shock wave analysis unit 180 may convert the electrical signal of the shock wave into a parameter related to frequency and amplitude.

The frequency measurement unit 182 of the shock wave analysis unit 180 may measure the common natural frequencies f1 and f2 in the first and second detectors 60 a and 60 b. For example, in (a) and (b) of FIG. 10 , the frequency measurement unit 182 may define the common natural frequencies of 8 kHz and 22 kHz from the shock waves detected by the first and second detectors 60 a and 60 b.

Referring to FIGS. 1 to 10 and 12 , the method S300 of determining the type and the size of the nanoparticles according to another embodiment of the present disclosure may include a step S310 of measuring an amplitude and a natural frequency in a shock wave. In the step S310, the controller 70 may measure the amplitude and the frequency of the shock wave based on a detection signal. In other words, in the step S310, the controller 70 may generate spectrum information of the amplitude depending on the frequency from the detection signal.

In the step S310, the amplitude measurement unit 184 of the shock wave analysis unit 180 may measure a magnitude of the amplitude at the natural frequencies f1 and f2. For example, as illustrated in (a) of FIG. 10 , the amplitude measurement unit 184 may measure the amplitude magnitude A1 a at the first natural frequency f1 as 0.015 and measure the amplitude magnitude A2 a at the second natural frequency f2 as 0.16 in the first detector 60 a. Further, as illustrated in (b) of FIG. 10 , the amplitude measurement unit 184 may measure the amplitude magnitude Alb at the first natural frequency f1 as 0.012 and measure the amplitude magnitude A2 b at the second natural frequency f2 as 0.004 in the second detector 60 b.

The method S300 of determining the type and the size of the nanoparticles according to another embodiment of the present disclosure may include a step S320 of calculating an amplitude ratio for each natural frequency in the plurality of detectors based on the measured amplitudes and natural frequencies.

In the step S320, the amplitude ratio calculator 186 may calculate the amplitude ratio for each natural frequency based on the analysis result of the shock wave analysis unit 180. For example, the amplitude ratio calculator 186 may calculate a first natural frequency amplitude ratio and a second natural frequency amplitude ratio based on the amplitude magnitudes measured by the amplitude measurement unit 184. The natural frequency amplitude ratio may indicate at least one of the first natural frequency amplitude ratio and the second natural frequency amplitude ratio. The “amplitude ratio for each natural frequency” may indicate a natural frequency amplitude ratio.

The first natural frequency amplitude ratio may refer to a ratio of the amplitude A1 a measured by the first detector 60 a to the amplitude Alb measured by the second detector 60 b, at the first natural frequency f1. For example, the first natural frequency amplitude ratio may be 0.015:0.012.

The second natural frequency amplitude ratio may refer to a ratio of the amplitude A2 a measured by the first detector 60 a to the amplitude A2 b measured by the second detector 60 b, at the second natural frequency f2. For example, the second natural frequency amplitude ratio may be 0.16:0.004.

The method S300 of determining the type and the size of the nanoparticles according to another embodiment of the present disclosure may include a step S330 of specifying the type of nanoparticles from the measured natural frequency and determining the size of the nanoparticles based on the amplitude ratio for each natural frequency.

In the step S330, the nanoparticle determination unit 188 may determine the type and the size of nanoparticles. The nanoparticle determination unit 188 may specify the type of nanoparticles based on the measured natural frequencies f1 and f2. In addition, the nanoparticle determination unit 188 may determine the size of the nanoparticles based on the amplitude ratio for each natural frequency for the specified nanoparticles calculated by the amplitude ratio calculator 186. That is, the nanoparticle determination unit 188 may specify the type of nanoparticles from the measured natural frequency, and compare the first and second natural frequency amplitude ratios calculated by the amplitude ratio calculator 186 with pre-stored data on the first and second natural frequency amplitude ratios for each type of nanoparticles to determine the size of the nanoparticles.

Referring to FIGS. 1 to 12 , the “amplitude ratio” may indicate at least one of the “detector amplitude ratio” and the “natural frequency amplitude ratio”.

The steps S220 and S320 of calculating the amplitude ratio may indicate at least one of the step S220 of calculating the amplitude ratio at the natural frequencies per the plurality of detectors and the step S320 of calculating the amplitude ratio per natural frequency in the plurality of detectors.

The steps S230 and S330 of specifying the type of nanoparticles from the measured natural frequency and determining the size of the nanoparticles based on the calculated amplitude ratio may indicate at least one of the step S230 of specifying the type of nanoparticles from the measured natural frequency and determining the size of the nanoparticles based on the amplitude ratio for each detector and the step S330 of specifying the type of nanoparticles from the measured natural frequency and determining the size of the nanoparticles based on the amplitude ratio for each natural frequency.

The present disclosure can determine more accurately a type and a size of nanoparticles by varying the distance between the plurality of detectors and the shock wave and determining the nanoparticles based on changes in the amplitude ratio for each natural frequency through this. The present disclosure can also improve the reliability of the determination results by using the detection results from the plurality of detectors.

Although the embodiments have been described with reference to a number of illustrative embodiments thereof, numerous other modifications and embodiments may be devised by those skilled in the art that will fall within the scope of the principles of the present disclosure. In particular, various variations and modifications are possible in the component parts and/or arrangements of the subject combination arrangement within the scope of the present disclosure, the drawings and the appended claims. In addition to variations and modifications in the component parts and/or arrangements, alternative uses will also be apparent to those skilled in the art. The scope of the present disclosure should be determined by rational interpretation of the appended claims, and all modifications within an equivalent scope of the present disclosure are included in the scope of the present disclosure. 

What is claimed is:
 1. A flow nanoparticle measurement device comprising: a flow cell configured to form a flow path through which a liquid sample flows; a laser generator configured to generate a first laser beam and irradiate the first laser beam to the flow cell; a plurality of detectors disposed at the flow cell and configured to detect a shock wave of a plasma induced by the first laser beam in the flow cell and generate a detection signal; and a controller configured to obtain the detection signal from the plurality of detectors and determine a type and a size of nanoparticles contained in the liquid sample based on the detection signal, the controller comprising: an amplitude measurement unit configured to measure an amplitude of the shock wave based on the detection signal; and a frequency measurement unit configured to measure a natural frequency of the shock wave based on the detection signal, wherein the plurality of detectors includes a first detector and a second detector that are disposed to be spaced apart from each other along the flow path, wherein the second detector is disposed further downstream in the flow path than the first detector, and wherein the controller includes: an amplitude ratio calculator configured extract at least one common natural frequency measured by the first and second detectors and calculate a natural frequency amplitude ratio that is a ratio of an amplitude corresponding to the common natural frequency in the first detector to an amplitude corresponding to the common natural frequency in the second detector; and a nanoparticle determination unit configured to specify the type of the nanoparticles based on data pre-stored in the controller and the common natural frequency and determine the size of the nanoparticles based on the data and the natural frequency amplitude ratio.
 2. The flow nanoparticle measurement device of claim 1, wherein the plurality of detectors are disposed to be spaced apart from each other along the flow path.
 3. The flow nanoparticle measurement device of claim 1, wherein the shock wave is generated at a set location in the flow cell; and the plurality of detectors are disposed to vary a distance from the set location.
 4. The flow nanoparticle measurement device of claim 1, wherein the controller determines the type and the size of the nanoparticles based on an amplitude and a frequency of the shock wave.
 5. The flow nanoparticle measurement device of claim 1, wherein the laser generator comprises: a laser generating device configured to generate a pulsed laser beam; a beam splitter configured to split the pulsed laser beam into the first laser beam and a second laser beam; and a lens disposed between the beam splitter and the flow cell and configured to adjust a focal length of the first laser beam, wherein the focal length is a distance between a focus of the first laser beam and the lens.
 6. The flow nanoparticle measurement device of claim 5, wherein the laser generator further comprises an energy detector facing the beam splitter and configured to measure a power of the second laser beam; and the second laser beam travels while forming an angle with the first laser beam, and is incident on the energy detector.
 7. The flow nanoparticle measurement device of claim 5, wherein the laser generator further comprises a beam block facing the flow cell and configured to block the first laser beam passing through the flow cell; and the flow cell is positioned between the lens and the beam block.
 8. The flow nanoparticle measurement device of claim 1, wherein the flow cell comprises: a flow portion that is a space formed inside the flow cell; a cell inlet connected to the flow portion, the cell inlet being an opening formed in the flow cell, the cell inlet through which the liquid sample is injected into the flow portion; and a cell outlet connected to the flow portion and spaced apart from the cell inlet, the cell outlet being an opening formed in the flow cell, the cell outlet through which the liquid sample is discharged from the flow portion.
 9. The flow nanoparticle measurement device of claim 8, wherein the flow portion comprises a main flow portion formed inside the flow cell; and the main flow portion is extended along one direction and passes a path of the first laser beam.
 10. The flow nanoparticle measurement device of claim 1, further comprising: a flow controller connected to the flow cell, disposed on a path of the liquid sample, and configured to control a flow velocity of the liquid sample.
 11. The flow nanoparticle measurement device of claim 10, wherein the flow controller comprises: a cylinder forming an inner space, the cylinder comprising an inlet member through which the liquid sample is introduced into the inner space, and an outlet member through which the liquid sample is discharged from the inner space, a piston disposed in the inner space and coupled to the cylinder so that the piston is able to reciprocate in parallel with one direction; an inlet valve positioned at the inlet member and configured to allow an introduction of the liquid sample and suppress a discharge of the liquid sample; and an outlet valve positioned at the outlet member and configured to allow the discharge of the liquid sample and suppress the introduction of the liquid sample.
 12. The flow nanoparticle measurement device of claim 11, wherein when the piston moves along the one direction and the inner space is pressurized, the inlet valve is closed and the outlet valve is opened; and when the piston moves along another direction opposite to the one direction, the inlet valve is opened and the outlet valve is closed.
 13. The flow nanoparticle measurement device of claim 12, wherein the flow controller further comprises: a cam spaced apart from the cylinder and forming a rotation shaft; and a connecting road having one end and other end, wherein the one end is rotatably connected to the cam at a location spaced apart from the rotation shaft, and the other end is rotatably connected to the piston, wherein when the cam rotates, the piston reciprocates in the inner space.
 14. A flow nanoparticle measurement method using a flow nanoparticle measurement device comprising a flow cell forming a flow path through which a liquid sample flows, a laser generator generating a pulsed laser beam and irradiating a first laser beam split from the pulsed laser beam to the flow cell, and a plurality of detectors disposed along the flow path and detecting a shock wave of a plasma generated in the flow cell to generate a detection signal, the flow nanoparticle measurement method comprising: measuring amplitudes at frequencies of the shock wave based on the detection signal; calculating an amplitude ratio based on the amplitudes and a natural frequency of the plurality of detectors; and specifying a type of nanoparticles contained in the liquid sample from the natural frequency and determining a size of the nanoparticles based on the amplitude ratio, wherein the step (S220, S320) of calculating the amplitude ratio comprises: a step (S320) of calculating an amplitude ratio per natural frequency at the plurality of detectors, wherein the amplitude ratio per natural frequency is a ratio of amplitudes at the natural frequency in the plurality of detectors. 